Red blood cell production in vetebrates results from the proliferation and differentiation of a sequence of progenitors arising from multipotential hematopoietic stem cells. Two erythropoeitic progenitor populations have been well characterized in the mouse: 1) the Burst-Forming Unit-Erythroid (BFU-E) population containing immature progenitors giving rise, within 7 days, to large multicentric erythroid colonies, in semi-solid cultures, called bursts; 2) the Colony-Forming Unit-Erythroid (CFU-E) population which is composed of more mature progenitors forming colonies of 8 to 64 red cells within 48 hours.
Two kinds of regulators control the differentiation of these erythropoietic progenitors. Erythropoietin (Epo), a hormone synthetized by the kidney, is required for CFU-E proliferation and differentiation whereas Burst-Promoting Activity (BPA) induces the development of BFU-E. This activity is shared by Interleukin 3 (IL3) stem cell factor, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) and Interleukin 4, (IL4).
Whereas Epo and IL3 are the major erythroid growth factors in vitro, other factors can also modulate the development of erythroid progenitors.
Patients suffering from chronic renal failure or anephric patients develop severe anemia and require regular blood transfusions with risk of hepatitis, iron overload and sensitization to major or minor histocompatibility antigens. The recent availability of recombinant human erythropoietin has allowed treatment of these patients with this hormone with significant results. It was however noticed that the large quantities of Epo given to the patients were less effective than the endogeneous Epo produced in those patients after renal transplantation.